Method and apparatus for predicting work of breathing

ABSTRACT

A method of creating a noninvasive predictor of both physiologic and imposed patient effort of breathing from airway pressure and flow sensors attached to the patient using an adaptive mathematical model. The patient effort is commonly measured via work of breathing, power of breathing, or pressure-time product of esophageal pressure and is important for properly adjusting ventilatory support for spontaneously breathing patients. The method of calculating this noninvasive predictor is based on linear or non-linear calculations using multiple parameters derived from the above-mentioned sensors.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part application of Ser. No.12/499,576, filed Jul. 8, 2009; which is a continuation application ofU.S. Ser. No. 11/758,159, filed Jun. 5, 2007, now U.S. Pat. No.7,588,543; which is a continuation application of U.S. Ser. No.10/652,992, filed Aug. 29, 2003, now U.S. Pat. No. 7,425,201; whichclaims the benefit of U.S. Provisional Application Ser. No. 60/407,099,filed Aug. 30, 2002, each of which is hereby incorporated by referenceherein in its entirety.

FIELD OF THE INVENTION

The present invention relates generally to the field of respiratorytherapy and physiology, including ventilator and respiratory monitortechnology, and, more particularly, to a method and apparatus forpredicting a patient's physiologic work of breathing and imposed work ofbreathing.

BACKGROUND

Mechanical ventilatory support is widely accepted as an effective formof therapy and means for treating patients with respiratory failure.Ventilation is the process of delivering oxygen to and washing carbondioxide from the alveoli in the lungs. When receiving ventilatorysupport, the patient becomes part of a complex interactive system thatis expected to provide adequate ventilation and promote gas exchange toaid in the stabilization and recovery of the patient. Clinical treatmentof a ventilated patient often calls for monitoring a patient's breathingto detect an interruption or an irregularity in the breathing pattern,for triggering a ventilator to initiate assisted breathing, and forinterrupting the assisted breathing periodically to wean the patient offof the assisted breathing regime, thereby restoring the patient'sability to breathe independently.

In those instances in which a patient requires mechanical ventilationdue to respiratory failure, sleep apnea, post-operative care, or othersituations, a wide variety of mechanical ventilators is available. Mostmodern ventilators allow the clinician to select and use several modesof inhalation either individually or in combination via the ventilatorsetting controls that are common to the ventilators. Some ventilatorssuch as those designed for noninvasive ventilation (NIV) primarilyutilize mask interfaces and can be very simple to operate with very fewchoices of settings, typically some baseline pressure level with orwithout a higher level of pressure support during inhalation.

The modes of breathing available in ventilators can be defined in threebroad categories: spontaneous, assisted or controlled. Duringspontaneous ventilation without other modes of ventilation, the patientbreathes at his own pace, but other interventions may affect otherparameters of ventilation including the tidal volume and the baselinepressure, above ambient, within the system. In assisted ventilation, thepatient initiates the inhalation by lowering the baseline pressure byvarying degrees, and then the ventilator “assists” the patient bycompleting the breath by the application of positive pressure. Duringcontrolled ventilation, the patient is unable to breathe spontaneouslyor initiate a breath, and is therefore dependent on the ventilator forevery breath. During spontaneous or assisted ventilation, the patient isrequired to “work” (to varying degrees) by using the respiratory musclesin order to breathe.

The total work of breathing (the work to initiate and sustain a breath)performed by a patient to inhale while intubated or attached to aventilator may be divided into two major components: physiologic work ofbreathing (the work of breathing of the patient, “WOBp”) and breathingapparatus (e.g., endotracheal tube or other form of patient interfaceand ventilator) imposed resistive work of breathing or imposed work ofbreathing (“WOBi”). The total work of breathing (“WOW”) can be measuredand quantified in Joules/L of ventilation. In the past, techniques havebeen devised to supply ventilatory therapy to patients for the purposeof improving patient's efforts to breathe by decreasing the total workof breathing to sustain the breath. Still other techniques have beendeveloped that aid in the reduction of the patient's inspiratory workrequired to trigger a ventilator system “ON” to assist the patient'sbreathing. It is desirable to reduce the effort expended by the patientin each of these phases, because a high total work of breathing load cancause further damage to a weakened patient or be beyond the capacity orcapability of small or disabled patients.

Furthermore, it is desirable to quantify the imposed work of breathing(WOBi) of a patient since this value is critical in the decision of whento extubate or remove ventilatory support from the patient. High workloads tend to create breathing patterns that are rapid and shallow (highfrequency and low tidal volume). Rapid shallow breathing is typically acontra-indicator of extubation success. If this high work load, however,is caused mainly by a large imposed work of breathing such that most ofthe excess work is caused by the breathing apparatus, extubation successis much higher

(“Elevated imposed work of breathing masquerading as ventilator weaningintolerance.” Chest October 1995; 108(4): 10215).

The early generation of mechanical ventilators, prior to the mid-1960s,was designed to support alveolar ventilation and to provide supplementaloxygen for those patients who were unable to breathe due toneuromuscular impairment. Since that time, mechanical ventilators havebecome more sophisticated and complicated in response to increasingunderstanding of lung pathophysiology. In an effort to improve apatient's tolerance of mechanical ventilation, assisted orpatient-triggered ventilation modes were developed. Partial positivepressure ventilation (PPV) support, in which mechanical supportsupplements spontaneous ventilation, became possible for adults outsidethe operating room when intermittent mandatory ventilation (IMV) becameavailable in the 1970s. Varieties of “alternative” ventilation modesaddressing the needs of severely impaired patients continue to bedeveloped. Similarly, small, easy to use ventilators have been developedto support patients who need less support. These ventilators oftenutilize noninvasive mechanisms (masks, nasal cannulas, full-head bags,etc.) to interface to the patient.

In recent years, microprocessors have been introduced into modernventilators. Microprocessor ventilators are typically equipped withsensors that monitor breath-by-breath flow, pressure, volume, and derivemechanical respiratory parameters. Their ability to sense and transduce“accurately,” combined with computer technology, makes the interactionbetween clinician, patient, and ventilator more sophisticated than ever.The prior art microprocessor controlled ventilators suffered fromcompromised accuracy due to the placement of the sensors required totransduce the data signals. Consequently, complicated algorithms weredeveloped so that the ventilators could “approximate” what was actuallyoccurring within the patient's lungs on a breath-by-breath basis. Ineffect, the computer controlled prior art ventilators were limited tothe precise, and unyielding, nature of the mathematical algorithms thatattempted to mimic cause-and-effect in the ventilator support providedto the patient.

The overall performance of the assisted ventilatory system is determinedby both physiological and mechanical factors. The physiologicaldeterminants, which include the nature of the pulmonary disease, theventilatory efforts of the patient, and many other physiologicalvariables, changes with time and are difficult to diagnose. Moreover,the physician historically had relatively little control over thesedeterminants. Mechanical input to the system, on the other hand, is to alarge extent controlled and can be reasonably well characterized byexamining the parameters of ventilator flow, volume, and/or pressure.Optimal ventilatory assistance requires both appropriately minimizingphysiologic workloads to a tolerable level and decreasing imposedresistive workloads to zero. Doing both should ensure that the patientis neither overstressed nor oversupported. Insufficient ventilatorysupport places unnecessary demands upon the patient's alreadycompromised respiratory system, thereby inducing or increasingrespiratory muscle fatigue. Excessive ventilatory support places thepatient at risk for pulmonary-barotrauma, respiratory muscledeconditioning, and other complications of mechanical ventilation.

In addition to total work of breathing (WOB), there are othermeasurements of patient effort, including power of breathing (POB), therate at which total work of breathing is done, and the pressure timeproduct (PTP), the integrated product of time multiplied by the decreasein pleural pressure during a breath. These methodologies are similar intheir goal of measuring patient effort, but are calculated differentlyand provide different measures of the patient effort.

Although total work of breathing (and its alternatives) has beenconsidered an important parameter for appropriately setting aventilator, it has remained largely unused because of the difficulty inobtaining its value. Physiologic work of breathing is defined using apleural pressure versus volume graph of a patient's breath. The pleurais a two-layered membrane that envelops the lung and containslubricating fluid between its inner and outer layers. During breathing,the respiratory muscles either compress or expand the lungs by exertingforces on the pleura. The pressure in the pleural space thereforerepresents the respiratory effort. The patient's physiologic work ofbreathing is the area from the chest wall compliance line on the rightto the pleural pressure versus volume loop on the left (see FIG. 1).Since the pleural pressure is very difficult to obtain and may bedifferent at different positions in the pleural space, a typicalsurrogate for pleural pressure is esophageal pressure. The esophagealpressure is typically obtained by placing a balloon in the esophagusbetween the heart and the stomach.

Likewise, although imposed work of breathing has been considered animportant parameter for appropriately setting a ventilator, it has alsoremained largely unused because of the difficulty in obtaining itsvalue. Imposed work of breathing is the area below baseline pressurecircumscribed within the tracheal pressure-tidal volume loop duringspontaneous inhalation. Typically, this is done by using a catheterinserted into the tracheal tube or a lumen in the side of the trachealtube that opens at the distal end of the tracheal tube. These devicesare then attached to a pressure transducer to measure tracheal pressure.The greatest single difficulty with these devices is the harshenvironment in which they exist and their propensity for becomingclogged. For this and other reasons, tracheal pressure is difficult toreliably measure and thus is not normally used.

U.S. Pat. No. 5,316,009 describes an apparatus for monitoringrespiratory muscle activity based on measuring resistance and elastanceof the lung and then calculating a value called Pmus from the standardequation of motion where Paw=Pmus+R*flow+V/C. It also disclosescalculation of a PTP of pmus, which is not the standard PTP, and a“work” Wmus, but not necessarily real WOB. A problem with the methodtaught by the '009 patent is that Pmus is difficult to measure in aspontaneously breathing patient because the parameters R and C must bevery accurately computed in order for Pmus to correlate with “work”.Moreover, R and C in a spontaneously breathing patient with ventilatorsupport are very difficult to obtain accurately.

Occlusion pressure at 0.1 seconds after breath initiation by the patient(PO.1) has also been proposed as an indicator of work of breathing. PO.1can be based on esophageal pressure or airway pressure. An esophagealpressure PO.1 is invasive but correlates fairly well with work ofbreathing. An airway pressure PO.1 is noninvasive, but does notcorrelate nearly as well with work of breathing.

A number of other patents exist for respiratory systems including U.S.Pat. Nos. 6,439,229; 6,390,091; 6,257,234; 6,068,602; 6,027,498;6,019,732; 5,941,841; 5,887,611; 5,876,352; 5,807,245; and 5,682,881,incorporated herein by reference.

Accordingly, there is a need in the art for a system and method tononinvasively and accurately predict physiologic work of breathing andimposed work of breathing in a patient. The present invention isdesigned to address this need.

SUMMARY OF THE INVENTION

Broadly speaking, the present invention provides a method and apparatusfor noninvasively predicting (estimating) physiologic work of breathing(the amount of effort expended by the patient to breathe) and imposedwork of breathing (the amount of effort expended by the patient imposedby the breathing apparatus). This effort, typically invasivelycalculated as (imposed and/or physiologic) work of breathing (WOB),power of breathing (POB), or pressure time product (PTP), is useful indetermining the most appropriate settings on a ventilator used tosupport the patient's breathing. Measuring patient effort allows forappropriate ventilatory support that avoids respiratory muscle fatigueand respiratory muscle deconditioning. Measuring imposed patient effortallows for more appropriate ventilatory support by allowing for theimposed effort to be driven to zero to simulate more natural breathingand also as an important extubation criteria.

In one aspect of the invention, the method comprises creating amathematical model of the patient's inspiratory effort usingpredetermined parameters that are collected noninvasively, such as thosecollected with standard respiratory monitors. The respiratory monitorstypically contain airway pressure and airway flow sensors that measurethe flow going into and out of the patient, and often times a carbondioxide sensor and pulse oximeter. From these time-waveforms, a varietyof parameters are selectively derived that are used in characterizingdifferent aspects of the patient's breathing and/or the patient'sinteraction with the ventilator. These parameters contain informationthat is extracted to accurately estimate the patient effort.

More specifically, the method of the invention comprises a method ofestimating the actual patient effort parameter using a combination ofmultiple parameters derived from sensors that monitor the patient and/orventilator. The patient effort parameter can be any parameter thatrepresents the effort exerted by the patient to breathe, including butnot limited to work of breathing, power of breathing, or pressure timeproduct.

In this method, the parameters are preferably derived from the airwaypressure, flow, and volume waveforms and the carbon dioxide and pulseoximeter waveforms normally collected by a respiratory monitor,including but not limited to tidal volume, breathing frequency, peakinspiratory pressure (PIP), inspiratory time, PO.1, trigger time,trigger depth, respiratory system resistance, respiratory compliance,end-tidal carbon dioxide, variations in the pulse oximeterplethysmogram, and the concavity/convexity of the pressure waveform.

This method includes using a linear combination of parameters or anonlinear combination of parameters, including but not limited to aneural network, fuzzy logic, mixture of experts, or polynomial model.Moreover, multiple different models can be used to estimate the patienteffort of different subsets of patients. These subsets can be determinedby various means, including but not limited to patient condition(pathophysiology), patient physiologic parameters (lung resistance andcompliance), or other parameters.

In a preferred aspect of the invention, the method for estimating workof breathing in a patient comprises use of a neural network, wherein theneural network provides work of breathing information for the patientbased upon input data, wherein the input data includes at least one ofthe following parameters: the airway pressure, flow, airway volume,carbon dioxide flow, and pulse oximeter plethysmogram waveforms normallycollected by a respiratory monitor, including but not limited to tidalvolume, breathing frequency, peak inspiratory pressure (PIP),inspiratory time, PO1 (see reference), trigger time, trigger depth,respiratory system resistance, respiratory compliance, end-tidal carbondioxide, variations in the pulse oximeter plethysmogram, and theconcavity/convexity of the pressure waveform, wherein the work ofbreathing information is provided as an output variable.

In the above-noted method, the neural network is trained by clinicaltesting of a test population of patients to obtain teaching data, whichincludes the above-noted input information. The teaching data isprovided to the neural network, whereby the neural network is trained toprovide an output variable corresponding to the work of breathing.Teaching data further includes esophageal pressure and/or trachealpressure.

As a system for estimating (imposed and/or physiologic) work ofbreathing in a patient, the system comprises a neural network that firstreceives as input primary teaching data obtained from clinical testingof a test population of patients, whereby the neural network learns theteaching data and is trained to provide an output variable for work ofbreathing, such that when the neural network receives patient input datain the form of the above-noted parameters obtained from a patient, theneural network provides the output variable for estimating work ofbreathing for that patient.

The invention can be implemented in numerous ways, including as a system(including a computer processing or database system), a method(including a computerized method of collecting and processing input dataand a method for evaluating such data to provide an output(s)), anapparatus, a computer readable medium, a computer program product, or adata structure tangibly fixed in a computer readable memory. Severalembodiments of the invention are discussed below.

As a system, an embodiment of the invention includes a processor unithaving input and output devices. The processor unit operates to receiveinput parameters, process the input and provide an output correspondingto work of breathing. This output can be then used to control externaldevices, such as a ventilator. The processing of the data can beaccomplished by various means such as neural networks, paralleldistributed processing systems, neuromorphic systems, or the like.

As a method of predicting (imposed and/or physiologic) work ofbreathing, the method includes processing predetermined input variables(parameters), preferably through the use of a neural network.

As computer readable media containing program instructions, anembodiment of the invention includes: computer readable code devices forreceiving input variables, processing the input, and providing an outputindicative of work of breathing. In a preferred embodiment, processingcomprises utilizing a neural network. The method may further includecontrolling a ventilator in response to the output obtained.

The methods of the present invention may be implemented as a computerprogram product with a computer-readable medium having code thereon. Theprogram product includes a program and a signal bearing media bearingthe program.

As an apparatus, the present invention may include at least oneprocessor, a memory coupled to the processor, and a program residing inthe memory that implements the methods of the present invention.

Other aspects and advantages of the invention will become apparent fromthe following detailed description taken in conjunction with theaccompanying drawings, illustrating, by way of example, the principlesof the invention.

All patents, patent applications, provisional applications, andpublications referred to or cited herein, or from which a claim forbenefit of priority has been made, are incorporated herein by referencein their entirety to the extent they are not inconsistent with theexplicit teachings of this specification.

BRIEF DESCRIPTION OF THE DRAWINGS

In order that the manner in which the above-recited and other advantagesand objects of the invention are obtained, a more particular descriptionof the invention briefly described above will be rendered by referenceto specific embodiments thereof which are illustrated in the appendeddrawings. Understanding that these drawings depict only typicalembodiments of the invention and are not therefore to be considered tobe limiting of its scope, the invention will be described and explainedwith additional specificity and detail through the use of theaccompanying drawings in which:

FIG. 1 is a graphical representation of pleural pressure showing elasticwork, stored energy of chest wall and resistive work;

FIG. 2 depicts the method of one aspect of the invention for a patienton a ventilator;

FIG. 3 depicts a graph of the nonlinear prediction of Power ofBreathing;

FIG. 4 depicts a neural network showing hidden layers; and

FIG. 5 depicts inputs and outputs of an adaptive system havingbackpropagation.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring now to the drawings, the preferred embodiment of the presentinvention will be described.

In the embodiment depicted in FIG. 2, a patient 10 requiring respiratorysupport and connected to a ventilator 12 will have an airway flow andpressure sensor 14, along with possibly a carbon dioxide detectorattached at the patient interface 11. Depending on the ventilator, anexpiratory limb and/or inspiratory limb 16 can be present. The patientinterface 11 can be invasive or noninvasive. For example, the patientinterface can be a tube, a nasal mask or cannula, nasal prongs/pillows,a face mask, or other device for providing ventilation to a patient.

These sensors, e.g., 14, measure the flow, pressure, and partialpressure of carbon dioxide in the gases that pass to and from thepatient. These raw signals 18 are preprocessed in a signal processor 20using analog and digital signal processing to clean the signal, removesensor biases and offsets, etc. These signals are then processed in aparameter extraction module 22 to calculate a variety of otherparameters from the flow, pressure, and CO2 data. For example, tidalvolume is computed by integrating the flow into the patient over aninspiratory cycle; peak inspiratory pressure is calculated bydetermining the maximum pressure during a breath; PO.1 is calculated bymeasuring the change in airway pressure during the first tenth of asecond of a breath; respiratory system resistance and compliance can becalculated by adaptively fitting a model, such as a linear model, to theairway pressure, flow, and volume signals; etc. In an aspect of theinvention, a neural network 24 may be provided to model the parametersso that a ventilator may be controlled through controller 26.

In order to create the model (training phase), patient information maybe collected from one or more patients. The methodology of obtaining thetest data (both input data and desired output data are used to create amodel that will predict patient effort) is as follows:

An inflatable balloon is placed into the patient's esophagus and acatheter is placed in the patient's trachea. The balloon is partiallyinflated and creates a closed circuit that transmits esophageal pressureto a pressure sensor connected to the end of a catheter connected to theballoon. The pressure sensors read the tracheal pressure and theesophageal pressure, which is a surrogate for pleural pressure (FIG. 1).The esophageal pressure drop during normal breathing is plotted on apressure-volume plot and a loop is created and integrated with a chestwall compliance line to calculate work of breathing. The esophagealpressure may be first cleaned of cardiac interference with an adaptivenoise cancellation technique that subtracts a scaled and shifted versionof the ECG or plethysmogram from the esophageal pressure. The chest wallcompliance can he calculated by paralyzing the patient and measuring theesophageal pressure rise in the circuit with a positive pressure breath.Many studies have found that 0.1 L1 cm H2O is an appropriate average.This plot is called the Campbell diagram and is a method for calculatingpatient inspiratory or physiologic work of breathing from the measuredesophageal pressure. For intubated patients, the imposed work ofbreathing may be calculated by integrating the tracheal pressure dropversus volume waveform similar to the total work of breathing (with theexception of the chest wall compliance). For both total and imposedefforts, power of breathing is calculated as a per minute average ofwork of breathing. Pressure Time Product (PTP) is measured just like WOBexcept using a Pressure-Time axis integration instead ofPressure-Volume. The work of breathing, (both physiologic and imposed),the power of breathing, and the pressure time product may be used asoutput variable for the system. These are the three main “desiredoutputs” of the preferred system. With patients using noninvasiveventilatory systems, the imposed work of breathing is not necessary forcalculating work of breathing, power of breathing, and/or pressure timeproduct.

Some of the inputs are standard parameters that are calculated in a verystraight forward manner, such as spontaneous breathing frequency (thenumber of breaths the patient takes per minute), tidal volume (thevolume of air inspired per breath), etc. Other input parameters are morecomplex, such as respiratory system resistance, compliance, and airwaypressure waveform characteristics. Resistance and compliance forexample, are typically calculated using a least squares modeling of thepressure, volume, and flow waveforms (obtained by a standard respiratorymonitor using airway pressure and flow sensors) using the equation:airway_pressure=flow×resistance+volume×compliance+positive_end_expiratory_pressure

Using the flow, volume, and pressure obtained from the flow and pressuresensors, the only unknowns are compliance and resistance and these canbe adaptively computed using techniques such as least squaresoptimization, as noted above.

The problem with these methods is that the equation is only valid if thepatient is not exerting any effort and the ventilator is responsible forall work of breathing. It has been experimentally determined that betterresults may be obtained by using an end-inspiratory pause and analyzingthe pressure drop with the cessation of flow (Δairway_pressure/Δflow) asresistance, and the Tidal_volume/(airway_pressure−PEEP) after flow hasceased for the compliance. This method, however, is also inaccuratesince often the patient's effort will disrupt the inspiratory pause. Inan aspect of the invention, a method of calculating resistance andcompliance may be based on examining the initial pressure rise duringthe very first few hundredths of a second for each breath. This initialpressure rise is related to only the flow entering the system as volumehas not yet accumulated in the lung, and thus reflects only theresistance. After resistance is accurately modeled, compliance can beobtained more accurately with the standard least squares techniquementioned above.

In certain embodiments, particularly those where input parameters arecollected via a non-invasive patient interface such as a mask or canulawhere circuit leaks are significant, compensation for leak flow is doneto derive accurate flow, volume, and CO2 waveforms. In certainembodiments, pressure waveforms must also be corrected. When the leak issignificant, the flow in and out of the patient is much different thanthat measured by the sensor since much of the air is lost through theleak. The goal of leak compensation is to accurately estimate the truevalues of the waveforms moving in and out of the patient. There arenumerous methods for correcting for leak in a flow waveform including,but not limited to, (a) equally redistributing the measured lost volumeover the breath and subtracting the bias flow from flow waveform, (b)calculating parabolic conductance and using the parabolic conductance tocorrect a measured flow waveform, (c) calculating the missing volumebetween inhalation and exhalation and allocating this volume throughoutthe breath, and (d) adjusting the flow waveform to minimize the averageflow. Leak correction modifies the flow, volume, and CO2 waveforms on asample by sample basis based on the parameters (e.g. parabolicconductance) calculated from the input waveforms. These parameters canbe calculated and adjusted continuously on a sample by sample basis, orcalculated periodically based on a windowing approach that may includeoverlap in the windows.

During data collection for the training data, the ventilator isadjusted; for example, the pressure support level may be adjusted andmeasured work of breathing and the other parameters are continuouslymonitored while changing the ventilator. Stable regions of the data aresaved and parameters are averaged over 1-2 minutes to reduce the noiseinherent in biological signals and the breath-to-breath variations.These averaged parameters are then used to create the model.

In an embodiment, the model, such as a neural network, is pretrainedwith clinical data and the input parameters can be collectednoninvasively with a standard respiratory monitor.

A neural network is trained to predict the physiologic and imposed WOB,POB, and PTP using the noninvasively acquired parameters described above(although invasive parameters may be added to the system, if desired.)Once a model having a desired degree of predictability has been achievedand verified, the esophageal pressure data (WOB, POB, PTP) is no longerneeded and the network output, such as an actual breathing effortvariable, may be used as an accurate predictor of patient effort.

Description of Neural Networks

Artificial neural networks loosely model the functioning of a biologicalneural network, such as the human brain. Accordingly, neural networksare typically implemented as computer simulations of a system ofinterconnected neurons. In particular, neural networks are hierarchicalcollections of interconnected processing elements (PEs). These elementsare typically arranged in layers, where the input layer receives theinput data, the hidden layers transform the data, and the output layerproduces the desired output. Other embodiments of a neural network canalso be used.

Each processing element in the neural network receives multiple inputsignals, or data values, that are processed to compute a single output.The inputs are received from the outputs of PEs in the previous layer orfrom the input data. The output value of a PE is calculated using amathematical equation, known in the art as an activation function or atransfer function that specifies the relationship between input datavalues. As known in the art, the activation function may include athreshold, or a bias element. The outputs of elements at lower networklevels are provided as inputs to elements at higher levels. The highestlevel element, or elements, produces a final system output, or outputs.

In the context of the present invention, the neural network is acomputer simulation that is used to produce a noninvasive estimate ofthe quantified patient effort described previously. The neural networkof the present invention may be constructed by specifying the number,arrangement, and connection of the processing elements which make up thenetwork. A simple embodiment of a neural network consists of a fullyconnected network of processing elements. As shown in FIG. 4, theprocessing elements of the neural network are grouped into the followinglayers: an input layer 30 where the parameters collected and/or derivedfrom the airway pressure and flow sensors are inputted to the network; ahidden layer or layers 32 of processing elements; and an output layer 34where the resulting prediction of patient effort 36 is produced. Thenumber of connections, and consequently the number of connectionweights, is fixed by the number of elements in each layer 30, 32, 34.

The most common training methodology for neural networks is based uponiterative improvement of the system parameters (normally called weights)by minimizing the mean squared difference between the desired output andthe network output (mean squared error, MSE). The input is applied tothe neural network, the neural network passes the data through itshierarchical structure, and an output is created. This network output iscompared with the desired output corresponding to that input and anerror is calculated. This error is then used to adjust the weights ofthe system so that the next time that particular input is applied to thesystem the network output will be closer to the desired output. Thereare many possible methodologies to adjust the weights, called thetraining algorithm. As shown in FIG. 5, the most common is calledbackpropagation that involves calculating each weight's responsibilityfor the error, and calculating a local gradient from this error in orderto use a gradient descent learning rule for each weight.

Based on the foregoing specification, the invention may be implementedusing computer programming or engineering techniques including computersoftware, firmware, hardware or any combination or subset thereof. Anysuch resulting program, having computer-readable code means, may beembodied or provided within one or more computer-readable media, therebymaking a computer program product, i.e., an article of manufacture,according to the invention. The computer readable media may be, forinstance, a fixed (hard) drive, diskette, optical disk, magnetic tape,semiconductor memory such as read-only memory (ROM), etc., or anytransmitting/receiving medium such as the Internet or othercommunication network or link. The article of manufacture containing thecomputer code may be made and/or used by executing the code directlyfrom one medium, by copying the code from one medium to another medium,or by transmitting the code over a network.

One skilled in the art of computer science will easily be able tocombine the software created as described with appropriate generalpurpose or special purpose computer hardware to create a computer systemor computer sub-system embodying the method of the invention. Anapparatus for making, using or selling the invention may be one or moreprocessing systems including, but not limited to, a central processingunit (CPU), memory, storage devices, communication links and devices,servers, I/O devices, or any subcomponents of one or more processingsystems, including software, firmware, hardware or any combination orsubset thereof, which embody the invention. User input may be receivedfrom the keyboard, mouse, pen, voice, touch screen, or any other meansby which a human can input data into a computer, including through otherprograms such as application programs.

All patents, patent applications, provisional applications, andpublications referred to or cited herein are incorporated by referencein their entirety, including all figures and tables, to the extent theyare not inconsistent with the explicit teachings of this specification.

Following are examples which illustrate procedures for practicing theinvention. These examples should not be construed as limiting. Allpercentages are by weight and all solvent mixture proportions are byvolume unless otherwise noted.

EXAMPLE 1 Prediction of Power of Breathing

With one particular subset of parameters (respiratory system resistance,compliance, tidal volume, and frequency), the present inventionpredicted power of breathing with a correlation coefficient well over0.90. Similar results were obtained with other combinations ofparameters. FIG. 3 shows a plot of predicted versus actual, or measured,power of breathing. A perfect prediction would be indicated by allvalues having identical x- and y-axis values, and thus would fall on thediagonal black line 40 shown in the FIG. 3. The wider the spread fromthis line, the lower the correlation between predicted and actual powerof breathing. In this particular prediction, data was obtained from 150patients collected at Shands Hospital at the University of Florida. Thedata was collected with multiple ventilator settings for each patient,thus giving us approximately 500 data points in the study.

EXAMPLE 2 Data for a Prediction (Table 1 Includes the First Data Points)

During data collection, respiratory measurements are made continuouslyand collected. These measurements are stored and later fed to the neuralnetwork for training. After the neural network model is trainedsuccessfully, the measurements from future are input to the “trained”model to produce a noninvasive prediction of actual power of breathing.This prediction of power of breathing is then used in a downstream fuzzylogic system that recommends changes to the ventilator.

In this example, the inputs/outputs to the system are:

-   Minute Ventilation—the total volume delivered to the patient per    minute (e.g. roughly tidal volume times breath frequency) in Liters.-   Trigger Gradient—the slope of the airway pressure drop due to the    patient effort that riggers the breath (e.g. before the ventilator    starts providing flow to the patient) in cm H2O per second.-   Pressure Rise Time—the time it takes for the flow to reach a maximum    and then decay to 80% of the maximum during a PSV(pressure support    ventilation) breath, as a proportion of total inspiratory time (no    units).-   Pmus using R Spike—the muscle pressure (as described in the patent)    using the resistance measurement from the initial time of pressure    rise (as described in the patent) and using the least squares    compliance (cm H2O*sec).-   Actual POE—the power of breathing (work per minute) measured    (Joules/min),-   Predicted POB—the power of breathing predicted by the system    (Joules/min).

These numbers were recorded continuously with data collection software.The values coming from the sensors are smoothed (time constant ofroughly 2 minutes) and analyzed continuously as known in the art. Whenno errors, artifacts, or transients are detected, a set of parameters islabeled as “suitable for prediction”, at one set of parameters perminute. These numbers are then collected and used to train the neuralnetwork. The neural network output is then used to optimally set theventilator based on the predicted power of breathing and other relevantpatient parameters (such as breathing frequency, tidal volume, andend-tidal CO2).

TABLE 1 Pressure Minute Trigger Rise pmus using R Actual PredictedVentilation Gradient Time Spike POB POB 8.2 14.2 0.8 63.4 3.2 4.1 7.16.4 0.7 40.7 2.6 2.7 8.5 15.3 0.8 72.9 5.9 6.2 11.9 9.5 0.8 81.2 6.5 6.27.9 8.0 0.9 37.7 4.6 5.8 7.7 12.4 0.9 64.3 7.2 6.5 8.4 13.4 0.5 51.5 2.12.1 7.8 8.1 0.7 79.4 3.8 3.4 4.9 15.2 0.8 41.5 5.5 5.0 6.3 26.3 0.8 41.45.4 5.7 6.1 2.3 0.7 37.3 1.5 2.0 11.0 15.4 0.9 83.5 8.9 9.0 9.9 7.5 0.774.2 2.0 3.2 4.5 8.1 0.8 47.3 3.8 3.2 5.6 3.4 0.7 21.8 1.6 2.3 6.3 12.00.9 77.0 6.4 5.8 11.7 11.2 0.8 66.4 6.5 7.0 3.1 12.9 0.7 31.3 2.8 2.47.1 2.0 0.7 15.0 2.9 2.3 8.0 7.4 0.7 79.5 3.8 3.4 7.8 4.4 0.7 22.1 2.62.5 12.1 26.3 0.8 179.2 13.4 11.4 6.3 6.4 0.7 21.4 2.2 2.7 5.7 18.3 0.831.1 5.3 5.4 7.8 10.9 0.5 73.9 3.1 2.5 8.1 6.1 0.8 56.5 4.3 3.7 7.0 16.60.8 69.5 5.0 5.6 4.6 13.5 0.7 26.9 4.0 3.0 6.9 10.9 0.8 29.4 3.5 5.0 4.814.0 0.8 39.7 5.3 4.8 8.2 33.5 0.5 95.5 1.7 2.8 9.9 11.4 0.8 35.6 6.95.9 5.6 18.5 0.6 30.2 4.6 3.7 5.5 12.1 0.8 49.5 5.5 4.9 8.1 12.4 0.882.0 3.8 4.3 6.5 16.0 0.9 46.0 3.4 5.4 11.5 16.7 0.8 45.9 9.1 9.7 7.99.3 0.8 59.0 3.9 4.7 9.1 7.6 0.6 47.4 1.5 2.5 8.5 4.0 0.6 32.0 1.7 2.26.2 13.6 0.6 33.1 5.1 3.3 7.1 21.6 0.8 77.6 5.7 5.2 8.3 13.7 0.9 87.68.3 6.8 6.6 25.2 0.8 38.8 4.8 5.7 6.4 19.2 0.7 36.5 5.1 5.1 12.5 12.80.9 93.4 9.2 9.9 8.9 14.7 0.7 71.2 3.1 3.9

It should be understood that the examples and embodiments describedherein are for illustrative purposes only and that various modificationsor changes in light thereof will be suggested to persons skilled in theart and are to be included within the spirit and purview of thisapplication and the scope thereof.

What is claimed is:
 1. A method for estimating effort of breathing of apatient, comprising: collecting noninvasive respiratory parameters ofthe patient, while receiving mechanical ventilation; calculating, usinga processor, respiratory data from the respiratory parameters; inputtingthe respiratory data into a mathematical model created using clinicaldata from a population of patients, where the clinical data includespleural pressure or a surrogate of pleural pressure; and generating atleast one output variable using the mathematical model corresponding toan estimated effort of breathing, wherein the estimated effort ofbreathing is an estimate of the patient's actual effort of breathingthroughout an entire breath, and wherein the at least one outputvariable is generated by the processor configured to run themathematical model.
 2. The method of claim 1 wherein effort of breathingrepresents a physiologic work of breathing and an imposed work ofbreathing.
 3. The method of claim 1 wherein the respiratory parameterscomprise one or more of airway pressure, airway flow, airway volume,carbon dioxide flow, leak flow, and pulse oximeter plethysmogram.
 4. Themethod of claim 3, wherein compensation for leak flow is performedbefore the respiratory data are calculated.
 5. The method of claim 4,wherein the compensation for leak flow is calculated from a stepselected from the group consisting of: (a) equally redistributing ameasured lost volume over a breath and subtracting a bias flow from ameasured flow waveform, (b) calculating a parabolic conductance andusing the parabolic conductance to correct the measured flow waveform,(c) windowing the calculation of parabolic conductance for real-timecorrection of the measured flow waveform, and (d) calculating theparabolic conductance using a breath detector that functions to detect astart and end of each breath to generate the parabolic conductance thatis applied to the measured flow waveform.
 6. The method of claim 1,wherein the mathematical model is selected from the group consisting ofa neural network model, a fuzzy logic model, a mixture of experts model,or a polynomial model.
 7. The method of claim 1, wherein the respiratorydata comprises one or more of tidal volume, breathing frequency, peakinspiratory pressure, inspiratory time, occlusion pressure at 0.1seconds after breath initiation trigger time, trigger depth, respiratoryresistance, respiratory compliance, end-tidal carbon dioxide, variationsin the pulse oximeter plethysmogram, and concavity/convexity of apressure waveform.
 8. The method of claim 1, wherein the mechanicalventilation is delivered via an invasive or noninvasive ventilator. 9.The method of claim 8, wherein the noninvasive ventilator comprises apatient interface assembly selected from the group consisting of: atube, a nasal mask, a nasal/oral mask, a total face mask, a nasalcannula, and nasal prongs/pillows.
 10. The method of claim 1, furthercomprising providing said at least one output variable from themathematical model to a ventilator to adjust a ventilator setting. 11.The method of claim 1, further comprising providing the output variablefrom the mathematical model corresponding to effort of breathing to adisplay.
 12. The method of claim 1, wherein the output variablecomprises one or more of a physiologic work of breathing variable, animposed work of breathing variable, a power of breathing variable, and apressure time product variable, each representing the effort exerted bythe patient to breathe.
 13. The method of claim 1, wherein themathematical model is a neural network trained to provide said at leastone output variable, wherein the training of the neural networkcomprises clinical testing of a test population of patients usingesophageal pressure as clinical data input to the neural network. 14.The method of claim 13, wherein a drop in esophageal pressure is plottedon a pressure-volume plot and a loop is created and integrated withchest wall compliance line to calculate inspiratory work of breathing asone of said output variables.
 15. The method of claim 14, wherein theapproximation of 0.1 L/cm H20 is used for chest wall compliance.
 16. Themethod of claim 14, further comprising calculating power of breathing asa per- minute average of work of breathing as one of said outputvariables.
 17. The method of claim 14, further comprising calculatingPressure Time Product (PTP) as one of said output variables.
 18. Themethod of claim 1, further comprising: classifying the patient; andselecting the mathematical model based on a classification of thepatient.
 19. The method of claim 18, wherein the patient is classifiedaccording to pathophysiology and physiologic parameters related to thepatient.
 20. The method of claim 19, wherein the physiologic parameterscomprise lung resistance and compliance.
 21. An apparatus for estimatingeffort of breathing of a patient, comprising: a processing device forcalculating respiratory data derived from noninvasive respiratoryparameters of a patient receiving mechanical ventilation, wherein thenoninvasive respiratory parameters comprise one or more of airwaypressure, airway flow, airway volume, carbon dioxide flow, leak flow andpulse oximeter plethysmogram, and wherein the respiratory data comprisesone or more of tidal volume, breathing frequency, peak inspiratorypressure, inspiratory time, occlusion pressure at 0.1 seconds afterbreath initiation trigger time, trigger depth, respiratory resistance,respiratory compliance, end-tidal carbon dioxide, variations in thepulse oximeter plethysmogram, and concavity/convexity of a pressurewaveform; a mathematical modeling device, created using clinical datafrom a population of patients, wherein the clinical data includespleural pressure or a surrogate of pleural pressure, to receive therespiratory data and predict effort of breathing; and an output signalthat provides at least one output variable from the mathematical modelcorresponding to effort of breathing.
 22. The apparatus of claim 21,wherein the mathematical modeling device is a neural network trained toprovide said at least one output variable, wherein the training of theneural network comprises clinical testing of a test population ofpatients.
 23. The apparatus of claim 21, wherein the output variablecomprises one or more of a physiologic work of breathing variable, animposed work of breathing variable, a power of breathing variable, and apressure time product variable, each representing the effort exerted bythe patient to breathe.
 24. The apparatus of claim 21, wherein themechanical ventilation is delivered via a noninvasive ventilator thatcomprises a patient interface assembly selected from the groupconsisting of: a tube, a nasal mask, a nasal/oral mask, a total facemask, a nasal cannula, and nasal prongs/pillows.
 25. A system forestimating effort of breathing of a patient, comprising: means forcollecting noninvasive respiratory parameters of the patient receivingmechanical ventilation, wherein the noninvasive respiratory parameterscomprise one or more of airway pressure, airway flow, airway volume,carbon dioxide flow, leak flow and pulse oximeter plethysmogram; meansfor calculating respiratory data from the respiratory parameters,wherein the respiratory data comprises one or more of tidal volume,breathing frequency, peak inspiratory pressure, inspiratory time,occlusion pressure at 0.1 seconds after breath initiation trigger time,trigger depth, respiratory resistance, respiratory compliance, end-tidalcarbon dioxide, variations in the pulse oximeter plethysmogram, andconcavity/convexity of a pressure waveform; means for predicting effortof breathing using a mathematical model created using clinical data froma population of patients, wherein the clinical data includes pleuralpressure or a surrogate of pleural pressure, that receives therespiratory data; and means for providing at least one output variablefrom the mathematical model corresponding to effort of breathing. 26.The system of claim 25, wherein the mathematical model is a neuralnetwork trained to provide said at least one output variable, whereinthe training of the neural network comprises clinical testing of a testpopulation of patients.
 27. The system of claim 25, wherein the outputvariable comprises one or more of a physiologic work of breathingvariable, an imposed work of breathing variable, a power of breathingvariable, and a pressure time product variable, each representing theeffort exerted by the patient to breathe.
 28. The system of claim 25,wherein the mechanical ventilation is delivered via a noninvasiveventilator that comprises a patient interface assembly selected from thegroup consisting of: a nasal mask, a nasal/oral mask, a total face mask,a nasal cannula, and nasal prongs/pillows.
 29. A non-transitory computerreadable medium for estimating effort of breathing of a patient,comprising: code devices for receiving measured noninvasive respiratoryparameters of the patient receiving mechanical ventilation, wherein thenoninvasive respiratory parameters comprise one or more of airwaypressure, airway flow, airway volume, carbon dioxide flow, leak flow andpulse oximeter plethysmogram; code devices for calculating respiratorydata from the respiratory parameters, wherein the respiratory datacomprises one or more of tidal volume, breathing frequency, peakinspiratory pressure, inspiratory time, occlusion pressure at 0.1seconds after breath initiation trigger time, trigger depth, respiratoryresistance, respiratory compliance, end-tidal carbon dioxide, variationsin the pulse oximeter plethysmogram, and concavity/convexity of apressure waveform; code devices for predicting effort of breathing usinga mathematical model created using clinical data from s population ofpatients, wherein the clinical data includes pleural pressure or asurrogate of pleural pressure, that receives the respiratory data; andcode devices for providing at least one output variable from themathematical model corresponding to effort of breathing.
 30. Thecomputer readable medium of claim 29, wherein the mathematical model isa neural network trained to provide said at least one output variable,wherein the training of the neural network comprises clinical testing ofa test population of patients.
 31. The computer readable medium of claim29, wherein the output variable comprises one or more of a physiologicwork of breathing variable, an imposed work of breathing variable, apower of breathing variable, and a pressure time product variable, eachrepresenting the effort exerted by the patient to breathe.